The Human-Milk Oligosaccharide Profile of Lactating Women in Dhaka, Bangladesh

Lisa G Pell, Eric O Ohuma, Chloe Yonemitsu, Miranda G Loutet, Tahmeed Ahmed, Abdullah Al Mahmud, Meghan B Azad, Lars Bode, Daniel E Roth, Lisa G Pell, Eric O Ohuma, Chloe Yonemitsu, Miranda G Loutet, Tahmeed Ahmed, Abdullah Al Mahmud, Meghan B Azad, Lars Bode, Daniel E Roth

Abstract

Background: Human-milk oligosaccharides (HMOs) are an abundant component of human milk that have health-related effects on breastfeeding infants. Since variation in HMO composition can be explained by maternal and environmental factors, understanding the diversity in HMOs across settings and identifying context-specific factors associated with HMO abundances is important.

Objectives: The aim was to describe the HMO profile of Bangladeshi women and to estimate the effect of maternal vitamin D supplementation on HMO composition.

Methods: In a cross-sectional analysis of data and samples from the Maternal Vitamin D for Infant Growth trial in Dhaka, Bangladesh (clinicaltrials.gov; NCT01924013), 192 participants were randomly selected including 96 from each of the placebo and highest-dose vitamin D supplementation groups. In mid-feed breast milk samples collected at a mean (±SD) postpartum age of 93 ± 7 d, absolute and relative abundances of 19 HMOs were analyzed by HPLC. "Secretors" were defined as participants with 2'fucosyllactose concentrations >350 nmol/mL. Associations between HMO concentrations and selected maternal or environmental factors were estimated by multivariable linear regression, adjusting for vitamin D group allocation and secretor status. HMO profiles of Bangladeshi women were compared with data from other international cohorts.

Results: Overall, 34% (65/192) of participants were nonsecretors. Secretor status was associated with the concentrations of total HMOs and 79% (15/19) of individual HMOs. Vitamin D supplementation did not affect the total or individual concentration of any measured HMO. 3-Fucosyllactose concentration was significantly higher in breast milk samples collected in December to February compared with samples collected in March to May. HMO composition was similar to other previously reported cohorts.

Conclusions: The HMO profile of Bangladeshi women is predominantly determined by secretor status. Context-specific HMO data may improve understanding of the effects of HMOs on the infant microbiome and health and guide the development of HMO-containing interventions.

Keywords: Bangladesh; breast milk; human-milk oligosaccharides; secretor status; vitamin D.

© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1
FIGURE 1
Flow chart of participant eligibility for inclusion and selection in the study. a MDIG trial group: dose of vitamin D3 supplementation given prenatally/postpartum.
FIGURE 2
FIGURE 2
Total and individual abundances of 19 HMOs among 192 Bangladeshi participants, overall and by secretor status. (A) Total HMO content and absolute abundance of 19 HMOs for all 192 cohort participants, by secretor status. (B) Relative abundance of 19 HMOs (%) for all 192 cohort participants, by secretor status. Each column in the 2 graphs displaying HMO absolute and relative abundances represents 1 individual participant, ordered from lowest to highest concentration of 2′FL. DFLac, difucosyllactose; DFLNH, difucosyllacto-N-hexaose; DFLNT, difucosyllacto-N-tetrose; DSLNH, disialyllacto-N-hexaose; DSLNT, disialyllacto-N-tetraose; FDSLNH, fucodisialyllacto-N-hexaose; FLNH, fucosyllacto-N-hexaose; HMO, human-milk oligosaccharide; LNFP I, lacto-N-fucopentaose 1; LNFP II, lacto-N-fucopentaose 2; LNFP III, lacto-N-fucopentaose 3; LNH, lacto-N-hexaose; LNnT, lacto-N-neotetraose; LNT, lacto-N-tetrose; LSTb, sialyl-lacto-N-tetraose b; LSTc, sialyl-lacto-N-tetraose c; 2′FL, 2′fucosyllactose; 3FL, 3-fucosyllactose; 3′SL, 3′-sialyllactose; 6′SL, 6′-sialyllactose.
FIGURE 3
FIGURE 3
Correlation and clustering between individual HMO concentrations, (A) overall and (B, C) by secretor status. The range of colors represents the Pearson correlation coefficients (r), which describe the strength (darker the color, the stronger the correlation) and direction (red/positive vs. blue/negative vs. white/no correlation) of the correlation between pairs of individual HMO concentrations. The distance (or lack of similarity) between each node and cluster in the dendrogram (A) was based on a dissimilarity index using Spearman correlation. Data above and below the diagonal line are identical. DFLac, difucosyllactose; DFLNH, difucosyllacto-N-hexaose; DFLNT, difucosyllacto-N-tetrose; DSLNH, disialyllacto-N-hexaose; DSLNT, disialyllacto-N-tetraose; FDSLNH, fucodisialyllacto-N-hexaose; FLNH, fucosyllacto-N-hexaose; HMO, human-milk oligosaccharide; LNFP1, lacto-N-fucopentaose 1; LNFP 2, lacto-N-fucopentaose 2; LNFP 3, lacto-N-fucopentaose 3; LNH, lacto-N-hexaose; LNnT, lacto-N-neotetraose; LNT, lacto-N-tetrose; LSTb, sialyl-lacto-N-tetraose b; LSTc, sialyl-lacto-N-tetraose c; 2′FL, 2′fucosyllactose; 3FL, 3-fucosyllactose; 3′SL, 3′-sialyllactose; 6′SL, 6′-sialyllactose.
FIGURE 4
FIGURE 4
Multivariable analysis of selected maternal and environmental factors and HMO composition among a cohort of 192 Bangladeshi women. The range of colors represents the direction and magnitude of the estimated effect size; all log-transformed HMO values were standardized by subtracting the HMO-specific mean from each HMO value and dividing by the HMO-specific standard deviation (equivalent to a Z-score) to allow for comparisons across different HMOs in multiple regression analyses. A separate multiple linear regression model was used to estimate each HMO-factor association, adjusting for vitamin D group and secretor status. One variable was marked with the “∼” symbol to indicate statistical significance after accounting for multiple testing using the Holm procedure. DFLac, difucosyllactose; DFLNH, difucosyllacto-N-hexaose; DFLNT, difucosyllacto-N-tetrose; DSLNH, disialyllacto-N-hexaose; DSLNT, disialyllacto-N-tetraose; FDSLNH, fucodisialyllacto-N-hexaose; FLNH, fucosyllacto-N-hexaose; HMO, human-milk oligosaccharide; LNFP1, lacto-N-fucopentaose 1; LNFP2, lacto-N-fucopentaose 2; LNFP3, lacto-N-fucopentaose 3; LNH, lacto-N-hexaose; LNnT, lacto-N-neotetraose; LNT, lacto-N-tetrose; LSTb, sialyl-lacto-N-tetraose b; LSTc, sialyl-lacto-N-tetraose c; 2′FL, 2′fucosyllactose; 3FL, 3-fucosyllactose; 3′SL, 3′-sialyllactose; 6′SL, 6′-sialyllactose.
FIGURE 5
FIGURE 5
Variation in the relative abundances of 19 individual HMOs in breast milk collected from lactating women who reside in 13 different geographic locations worldwide, overall (A) and by secretor status (B, C). Data generated from women in the Canadian CHILD Cohort study were previously published by Azad et al. (17). Data generated from women in all other settings, with the exception of Bangladesh, were previously published by McGuire et al. (18) *“W&I” is used to describe a cohort from southeastern Washington and northwestern Idaho, USA. DFLac, difucosyllactose; DFLNH, difucosyllacto-N-hexaose; DFLNT, difucosyllacto-N-tetrose; DSLNH, disialyllacto-N-hexaose; DSLNT, disialyllacto-N-tetraose; FDSLNH, fucodisialyllacto-N-hexaose; FLNH, fucosyllacto-N-hexaose; HMO, human-milk oligosaccharide; LNFP1, lacto-N-fucopentaose 1; LNFP II, lacto-N-fucopentaose 2; LNFP III, lacto-N-fucopentaose 3; LNH, lacto-N-hexaose; LNnT, lacto-N-neotetraose; LNT, lacto-N-tetrose; LSTb, sialyl-lacto-N-tetraose b; LSTc, sialyl-lacto-N-tetraose c; 2′FL, 2′fucosyllactose; 3FL, 3-fucosyllactose; 3′SL, 3′-sialyllactose; 6′SL, 6′-sialyllactose.

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